Multidose dispenser for sterile liquid preparations

ABSTRACT

A bottle or container suitable for the sterile storage of liquid products therein and the administration therefrom of said products dropwise, the sterility being maintained even after first opening the bottle, without the need to include preservatives in the liquid product. The dispenser comprises a container body ( 1 ), a capsule ( 3 ) and a dropper assembly ( 2 ), ending with a rigid dropper nozzle ( 5 ) provided with one or more transversal ports communicating with the interior of the container body ( 1 ), covered by a resiliency deformable tubular sleeve ( 9 ). The dropper nozzle comprises a first portion having a smaller conicity ( 6 ) making out the distal end of the dropper and a second portion having grater conicity ( 7 ) on which three of such ports are preferably provided. The closure capsule ( 3 ) comprises an internal projection ( 21 ) which comes into contact, when the capsule is closed, with the tubular sleeve ( 9 ) at the position where the second portion having grater conicity ( 7 ) of the dropper nozzle is located.

The present invention concerns a multidose bottle for dispensing liquidpreparations without preservatives. More specifically, the inventionconcerns a container specially designed for the sterile conservation ofliquid products therein and their distribution in the form of drops, thesterility being maintained also after the first opening of thecontainer, without the need to include preserving agents in the liquidproduct.

Many products, particularly but not exclusively in the medical field,are obtained and used in liquid form, such as solutions or mixtures ofone or more liquid components with one or more dissolved solids; fortheir proper application, these liquids must be dispensed dropwise atthe time of use. The most common example is that of liquidpharmaceutical products, both for systemic administration (oral drops)and more frequently for topical administration, such as on the nasal ororal mucosa, in the auricle of the ear and, above all, in theconjunctival sac. Topical ophthalmic products, such as eye-drops andartificial tears, also have the peculiarity that, besides needing to beadministered in the form of drops, they must also be applied by theusers on their own visual apparatus, and thus normally require the useof droppers with sufficiently elongated nozzles to facilitate as much aspossible the actual application of the medication onto the surface ofthe cornea.

Other examples of liquid products that may require storage in vials orbottles and distribution in the form of drops are particular detergentsor additives, also outside the pharmaceutical field, such as in thefield of cosmetics or foodstuffs. These fields also have the problem ofproperly storing liquid products in sterile conditions and withoutaltering their quality from one use to the next, and also in thesefields, for particular applications, there may be required a dropwisedispensing of the product which may be as uniform and easilycontrollable as possible.

The conventional way of preventing or combating the microbial growth inliquid products to be used several times over after the first opening ofthe relative container consists of adding suitable preserving agents,antioxidants and antibacterial agents in the liquid product itself. Thechoice and concentration of the agents used must in any case be such toguarantee the necessary sterility within the envisaged conditions andexpiry date of the product life, and at the same time must not alter theinherent characteristics of the liquid product.

More specifically, with reference to products for ophthalmic use thatare packaged in multidose bottles of flexible material, the initialsterilization of the product takes place during the bottling phase,after which the bottle is sealed and packaged, and arrives in theconsumer's hands in sterile form. When the bottle is first opened, theproduct would still be in a sterile condition, also without the use ofpreserving agents. On first use, by gently squeezing the bottle someliquid is forced out and made to pass through the dropper nozzle toreach the user. When the pressure exerted on the bottle ceases, thebottle stops dispensing the product; however, due to the elasticity ofthe material used, as soon as the pressure on the bottle ceases, thebottle returns to its original shape and reintegrates the volume ofliquid dispensed by sucking in air from the outside environment throughits nozzle. This air, which is potentially polluted, contaminates theremaining liquid in the bottle by starting an oxidative process on thevolume of product left inside. This contaminating activity exerted bythe outside air is normally prevented by using preservatives orantioxidants: without these, the pharmaceutical product could only beused once because the remaining liquid would become irreparably alteredand unusable. All this would be considerably worsened if, duringadministration, the dropper came into contact with the user's body,which may potentially be contaminating.

Unless an alternative administration method is used—something which canonly be economically justifiable in certain cases—namely the use ofsingle dose packages containing a quantity of product for just oneapplication, which do not require any preservatives, in the other casesthe use of preservatives and antioxidants in multidose bottles intendedto contain sterile preparations is made essential in view of a number offeatures that the product has to maintain over time, and especiallyafter the container is first opened. These features include the capacityto maintain the liquid in sterile conditions after the bottle is firstopened, and also when non-sterile air is sucked back in to replace theliquid used and, in addition, in the case of accidental contact betweenthe dropper and parts of the user's body that may be polluting. Suchfeatures also include the capacity to resist oxidation due to contactwith the outside air that increasingly replaces the volume of liquidused, and this throughout the useful life of the product once the bottleis first opened.

The addition of preservatives to liquid products for ophthalmic use,although admitted in the pharmacopoeia and commonly accepted, is notdevoid of a series of drawbacks, however. These include, in particular,the possibility of causing burning sensations or inflammatory orallergic reactions as well as, above all, the proven cytotoxicity ofthese products. For example, it is well-known that some preservativesused for ophthalmic products have a toxic effect on the goblet cells ofthe cornea, so that their prolonged use could cause more problems thanthe ones they can actually help to overcome.

One possible strategy to avoid using preservatives in multidose bottlesof liquid products is to provide one or more antibacterial filters onthe liquid pathway towards the exit point in the bottle, in particular,filters with openings or pores of about 0.2 micron in diameter, whichmechanically prevent any micro-organisms from passing through them,while not preventing the flow of liquid out. Examples of devices usingsuch solution are disclosed in the international patent applicationpubl. No. WO 90/05110 (Eye Research Institute of Retina Foundation),concerning a multidose bottle equipped with a pair of filters, onehydrophilic and the other, more downstream, water-repellent, placedalong the liquid outward path, and in the U.S. Pat. No. 5,105,993 (LaHaye Laboratories), employing an antibacterial filter placed inside thedropper nozzle, which also employing a further filter placed on aventing port in the bottle. It is obvious that the adoption of anantibacterial filter, does not avoid that the section of the dropperduct lying downstream of the filter is still exposed to contamination bythe external environment.

Still in the specific field of pharmaceutical products for topical use,U.S. Pat. No. 5,232,687 (Ursapharm) proposes adopting another,alternative or complementary, device in order to guarantee the sterilityof a liquid product for topical administration without resorting topreservatives: the use of a solid substance with a germicide action likesilver. The device proposed to this aim is in practise a smallreciprocating pump spray dispensing metered amounts of liquid product.During the passage through a dispensing chamber, the product must comeinto close contact with a silver-based element with germicide functions.In this case, any inflowing of air inside the product container is notallowed by the fact that the small pump is made airtight.

Another commercially available device for dropwise dispensing liquidpharmaceutical products not requiring the use of preservatives isdescribed in U.S. Pat. No. 6,336,571 (Laboratoires Théa), where acontainer with flexible bellow-shaped walls is used, protected by anexternal rigid shell, that is removable in order to allow access to thebellow-shaped bottle containing the liquid during the administration.Also in this case, the necessary aseptic conditions are provided by anantibacterial filter placed along the product outflow path.

A further solution for manufacturing multidose dispenser bottles forliquid products without preservatives is described in European patentapplication EP-A-1319606 (Nihon Tenganyaku Co. and Taisei Kako Co.),which concerns a double-walled container with an external flexible walland an internal collapsible one, in which the manually exerted pressureon the external container is transmitted to the internal wall therebyforcing the liquid out during administration. Then, due to the presenceof a vent hole on the external container, the latter can elasticallyreturn to its original shape by sucking air into the gap between theexternal wall and internal collapsible wall. This air does not come intocontact with the product enclosed inside the internal container, thuspreventing any possible contamination to the product itself.

The outflow of the product from the bottle occurs through a check valvethat does not allow the liquid to come back into the container, butdownstream of this check valve the liquid still passes through anantimicrobial filter before leaving the container. Also in this case,therefore, the device includes a space between the check valve and thedropper tip on which the filter is located, wherein some stagnantliquid, which is not excluded from contact with the outside air, is lefteven if it should be protected from the entrance of micro-organisms.

In general, the known devices envisaging the presence of check valves onthe liquid outflow duct from the bottle still have sections downstreamof the check valve, which may particularly include the dropper nozzle,where stagnant liquid remains after administration and wherecontaminating air can enter from the outside.

A dispenser bottle for products in drops without preservatives, providedwith a check valve realised directly onto the dropper nozzle, operatingon the dropper tip itself and automatically activated at the end of thepressure exerted by user on the container body, is described in theinternational patent publ. No. WO2006/043295 (of the same applicants).The device includes a dropper nozzle designed with a pin plug having afrusto-conical shape, complementary to the nozzle shape, wherein,however, the valve element having the plug function is fixed withrespect to the bottle body, and the element having the function of thecorresponding seat, namely the nozzle, is displaceable. The terminallower part of nozzle, where the latter joints the bottle therebyblocking it in an airtight manner, includes an annular membraneexpansion chamber sufficiently flexible to allow the dropper nozzle toextend forward with respect to the fixed plug when the pressure on theliquid contained in the bottle increases as a result of a pressureexerted on the outside of the bottle. The slight forward displacement ofthe nozzle with respect to the fixed plug opens around said plug a gapsufficiently wide to allow the passage of the liquid to be dropwisedispensing, which flows out from the nozzle tip. As soon as theexternally applied pressure ceases, the annular membrane contractsagain, automatically causing the nozzle to draw back with respect to thefixed pin plug.

In the disclosed device, the closure of the dropper after administrationis automatic and, above all, it occurs exactly on the dropper tip,without leaving liquid residues in intermediate positions within thedispenser. However, the device that can be produced according to theteaching of the said document suffers from some manufacturingcomplexity, firstly because the bottle has to be produced with a doublewall, with a collapsible container for the product inside and a bottlemade of flexible material outside, with an air gap there between.

Based on such prior art, therefore an object of the present invention isto provide a dispenser device for products in drops which, while notrequiring the addition of preservatives in the product, is able toprotect the product from the entrance of polluting agents in the droppernozzle, constituting the terminal supplying element, thus preventing notonly air from entering from outside, but also the presence of inactivevolumes and stagnation zones within the device, so as to avoid that thedropper interior remains not protected and moist with product.

Besides the pin plug valve described above, another kind of device forstopping and regulating the product flow from a dispenser of the samekind as those here at issue which allows to obtain the closure of thedispensing conduit in the most external point of the nozzle, with nozones of liquid stagnation or zones where potentially polluted air mayreturn or stay, after the supply, is the unidirectional flow valve oftenrefer to as sleeve valve. This is normally made of a flexible sleevemade of an elastomeric material or a material resiliently stretchable,such as silicone rubber, which surrounds a rigid tubular projection,having a generally cylindrical or conical shape (nozzle), directlycommunicating with the bottle interior on which some apertures arepresent for the product to be administered. The apertures are normallytwo or more radially extending ports provided on the rigid projection;said ports are generally closed by the resilient sleeve, but they allowliquid to flow outward from the interior of the container when asufficient pressure is exerted on it so as to counter the radialpressure of the resilient sleeve, the latter being normally pre-loadedand adhering to the tubular projection forming the nozzle. As soon asthe dispensing pressure is released, the sleeve resiliently returns toclose the ports for the liquid passage, and inactive zones around thesleeve are left where some non-dispensed liquid may remain or air orpolluted material from the exterior may return.

An example of a dispensing device suitable for medicaments or otherliquid products which must be preserved from contamination or protectedfrom oxidation in spite of the repeated and protracted use is disclosedin the European patent application EP-A-172711 (The Boots Company),concerning a collapsible container for liquid medicaments or similar,where in the product is dispensed through a resilient sleeve valvecooperating with the substantially cylindrical nozzle, which is incommunication with the container interior and is provided with suitableradial apertures. Since the sleeve valve system alone cannot guaranteeagainst abnormal accidental pressures excreted on the bottle, whichwould result in undesired outflow of liquid, the device is also providedwith a closure element, consisting of a cap (in the case shown, a snapcap) which surrounds and encloses the dispensing nozzle and presses,with an internal projection of the cap itself, the terminal portion ofthe dispensing nozzle, close to the tip thereof.

The device concerned, as well as other known devices, where a liquidsupply occurs through a resilient sleeve valve are combined, in order toprevent the accidental leakages of the liquid contained in the bottle,with closure systems (caps or capsules) wherein a rigid element exerts apressure against the nozzle tip where the resilient sleeve is present,which represents the spontaneous closure zone of the sleeve system.

In view of the foregoing, according to the present invention there hasbeen devised a bottle or container for liquid products to beadministered dropwise which is particularly suitable for the packagingof multidose pharmaceutical liquid products without preservatives,equipped with a dispensing system with unidirectional flow sleeve valve,which is suitable to insure the outmost asepticity to the productcontained therein, having an improved performance in comparison with theknown devices of the same kind. Actually an improved performance hasbeen obtained both from the point of view of a reliable size control ofthe dispensed drops and from that of preventing from the possibleaccidental outflow of the product, due to an abnormal mechanicalpressure on the bottle.

The regularity in volume of each drop of dispensed product, as well asthe ability not to give rise to sprays or to continuous jets of productwhen the bottle is too energetically squeezed, are extremely importantaspects in the pharmaceutical field. This is the case, for instance, ofthe drop-wise dosing of a product like an antibiotic collyrium or anoral paediatric solution, where an irregular size of the drops resultsin uncontrollable variations of the administered dosage. On the otherhand, as already noted, the possibility of accidental outflow of productbrings about, in addition to a loss of product, the pollution of theexternal zone surrounding the nozzle, with some liquid stagnating, forinstance, between the nozzle and the external capsule.

In order to prevent the occurrence of similar shortcomings, the presentinvention proposes, as a first measure, to realize the rigid projectionmaking out the dispensing nozzle, on which the elastomeric materialsleeve is to be placed, with at least two subsequent portions havingdifferent conicity: namely, a first portion more tapered (i.e., with agreater conicity) closer to the body of the bottle and bearing the portsfor the passage of the product contained in the bottle, and a secondportion in a terminal position, with a lesser conicity, making out theproper tip of the dropper nozzle, the resilient sleeve extending in sucha way as to cover both said portions. The portion with lesser conicity,which makes out the elongated dropper tip, is shaped in such away as tonever come into contact with other elements of the same device, so thatthe elastomeric material sleeve does not undergo any disturbance in thepoint where it is more delicate. The intermediate portion with greaterconicity, i.e. the portion where the ports for the passage of productfrom the bottle interior are provided, is also the portion where theinternal closure element of the cap abuts. Thus, the contact between thecap and the elastomeric sleeve does occur on the dropper tip, rather inthe more tapered intermediate section, where the sleeve is moreresistant to stresses that might tear it or deform it, and where aclosing action on the ports for the liquid passage is directly exerted,such ports actually being located in that position in the dropper.

Therefore, the present invention specifically provides a dispenser forliquid preparations without preservatives, comprising a container body,a dropper assembly, and a closure capsule suitable to be coupled withsaid dropper assembly, wherein the dropper assembly in turn comprises aclosure element for the container body ending with a rigid droppernozzle provided with one or more transversal passage ports,communicating with the interior of said container body covered with aresiliently deformable tubular sleeve, co-operating with said ports forintercepting a liquid preparation contained in said dispenser,characterized in that the said dropper nozzle comprises at least twoportions to axially subsequent portions having different conicity: afirst portion with smaller conicity making out the distal of saiddropper nozzle and a second portion with grater conicity on which saidtwo or more ports are provided, and in that said closure capsulecomprises an internal projection that comes into contact, when thecapsule is closed, with said resiliently deformable tubular sleeve at aposition corresponding to the second portion of the dropper nozzle withgrater conicity, thereby blocking the possible passage of the liquidpreparation through the said two or more ports.

According to some preferred embodiment of the invention, the dropperassembly further comprises a protective tubular element coaxial with thedropper nozzle, which extends outside the tubular sleeve in such a wayas to surround it for most of its length, so as to protect it accidentalcontacts with the exterior when the closure capsule is not present, thatis when the package is open and the device is in use.

Preferably, the said resiliently deformable tubular sleeve (or sheath)comprises a first portion and a second axially subsequent portion,corresponding to said first and second portion of the dispensing nozzle.Also these portions, following the shape of the nozzle on which thesleeve is mounted, may have two sections with different conicity, andmay also have different thickness, the smaller thickness being possiblyreserved to the sleeve portion corresponding to the distal end of thedropper. As it will be clear with reference to the enclosed drawings,different tapering degree of two sections of dispensing nozzle causesthe liquid dispensed by the device, which must overcome the pressureexerted by the sleeve which becomes radially dilated, once the firstsection with grater conicity is passed, flows much more easily in thenozzle portion with smaller conicity. As a result, the dispensingfunction is very well regulated as a portion of the pressure exerted bythe user's fingers on the dispenser body.

According to some preferred embodiments of the invention, the resiliencydeformable tubular sleeve comprises, at its end facing the containerbody, a third portion having a grater thickness than the previous ones,ending in an annular projection. The latter is coupled with the end ofthe cited protective tubular element facing towards the container body,so that the protective tubular element blocks the resilient sleeve inits seat, preventing it from slipping off the dispensing nozzle.

Preferably, the tubular protective element is also provided with anintermediate flange which is fixedly blocked on said closure element ofthe container body, in such a way that the same tubular protectiveelement cannot slip off the dispenser when the latter is in use.

As noted, the liquid contained in the multidose dispenser according tothe invention, under the effect of a manual pressure exerted on thecontainer body, passes through the said two or more ports provided onthe first portion with the greater conicity of the dispensing nozzle andflows within the resilient sleeve thereby reaching the dispensingnozzle. In order to obtain a distribution as homogeneous as possible ofthe dispensed liquid said portions are three in number, placed at 120°one from the other around the periphery of the nozzle.

As the other devices of the prior art the dispenser according to theinvention may have a single-walled container body of the bottle type,made of flexible resilient material. As an alternative, it may be of thedouble-walled type with a collapsible internal container and an air gapplace there between, or else it may be of the single-walled collapsibletube type. In the latter case, the tube may be provided with aconventionally shaped cap, or with cap allowing it to be placed upsidedown (“top-down” tube container).

The preferred embodiment, both in view of its practicality of use and inview of its cheapness and ease of realization at an industrial level, isthe single-walled type bottle made of resiliently flexible material. Inthis case, the presence of the double-walled container with the internalair gap may be avoided thanks to the use of a venting valve withhydrophobic membrane for the passage of the gases only from and into thebottle, of the same type of the membranes available on the market withthe commercial name Gore™. Preferably, the hydrophobic membrane has aporosity of 0.2 μm, so as to function also as mechanical filter againstthe micro-organisms possibly carried with the air sucked in through thevalve in replacement of the volume of liquid product dispensed.

The venting valve with hydrophobic membrane has a substantiallycylindrical shape and it is housed, according to a preferred embodimentof the invention, in a suitable seat within the closure element of thecontainer body, which is included in the dropper assembly.

The dispenser according to the invention is also completed by anexternal closure capsule suitable to couple with the dropper assemblydescribed above, and which preferably comprises a screw cap suitable toprotect the said dropper nozzle and an external knurled overcap outsidethe screw cap and connected to it. The combination of screw cap andovercap creates a safety closure system that prevents accidental openingof the bottle, like the kind of devices normally used on pharmaceuticalbottles to avoid any improper use by children (child-proof devices). Inaddition, the capsule envisages a part frangible on first opening thebottle acting as a guarantee seal (tamper-evident device).

The specific features of the present invention, as well as itsadvantages and corresponding operating modalities, will be more evidentfurther on with reference to a specific embodiment of the invention,illustrated merely for exemplary purposes in the attached drawings,wherein:

FIG. 1 shows a longitudinal cross-section of a multidose dispenser forliquid preparations according to the present invention, particularlydesigned for dispensing pharmaceutical products drop by drop withoutusing preservatives, and complete with all its closure elements;

FIG. 2 shows a longitudinal cross-section of the same bottle of FIG. 1,without the external closure capsule;

FIG. 3 shows a longitudinal cross-section of the closure capsule of thesame dispenser;

FIGS. 4A and 4B respectively show a longitudinal cross-sectional viewand a lateral view of the closure element of the container body, whichis the main element of the dropper assembly of the dispenser of theprevious figures;

FIG. 4C is a top plan view of the same element of FIGS. 4A and 4B;

FIG. 4D shows a perspective view of the same element of FIGS. 4A-4C;

FIGS. 5A, 5B, and 5C, respectively show a longitudinal cross-sectionalview, a lateral view and a perspective view of the tubular sleeve of thedropper assembly of the dispenser shown in the previous figures;

FIGS. 6A, 6B, and 6C, respectively show a longitudinal cross-sectional,a top plan view and a perspective view of the tubular protective elementof the dropper assembly of the dispenser shown in the previous figures;

FIGS. 7A, and 7B, respectively show a longitudinal cross-sectional viewand a perspective view of the venting valve element with hydrophobicmembrane (Gore™) of the dropper assembly of the dispenser shown in theprevious figures;

FIG. 8A shows a longitudinal cross-sectional view of the cap thatconstitutes an element of the closure capsule of the dispenser of FIG.1;

FIGS. 8B, and 8C, respectively show a top plan view and a perspectiveview of the same cap of FIG. 8A;

FIG. 9A shows a longitudinal cross-sectional view of the overcapconstituting an element of the closure capsule of FIG. 1;

FIGS. 9B and 9C respectively show a top plan view and a perspective viewof the same overcap of FIG. 9A;

FIG. 10 shows a schematic view, in cross-section and partially brokenaway, of the dispenser of FIG. 1, with the cap constituting an elementof the closure capsule but without the overcap; and

FIG. 11 shows schematic view in longitudinal cross-section and partiallybroken away of the same dispenser of FIG. 10, without the cap.

As it is shown in the overall views of FIGS. 1, 2 and 3, as well as inthe schematic drawings of FIGS. 10 and 11, the illustrated embodiment ofdispensing device for liquid products according to the inventionconsists of a container body (1) closed on top by a dropper assembly (2)and completed by a closing capsule (3). The dropper assembly (2), whichis also shown in greater detail in FIGS. 4A-D, 5A-C, 6A-C and 7A-B,comprises in turn a closure element (4), individually shown in FIGS.4A-B, consisting in a single piece of moulded plastic material. Thelatter ends in a rigid dropper nozzle (5), having a frusto-conical shapewith a lesser conicity in its terminal end portion (6) and more taperedin the intermediate portion (7). The terminal portion (6) is full, whilethe intermediate portion (7) is internally hollow and communicates withthe interior of the container body (1), being provided with three ports(8) radially placed at 120° around its periphery.

The second main element of the dropper assembly (2) consist of a tubularsleeve (9) made of elastomeric material, in particular silicone rubber,surrounding the dropper nozzle (5) both at the level of the terminalportion (6) at the level of the intermediate portion (7) with graterconicity. Besides FIGS. 1-3, and 10, 11, the tubular sleeve (9) isindividually shown in FIGS. 5A-C.

In the embodiment shown herein, the resilient tubular sleeve (9)comprises three separate portions with different conicity and thickness,of which the terminal portion (10) having a smaller thickness is the onecovering the terminal portion (6) of the dropper nozzle (5), theintermediate portion (11) is the one covering the intermediate portion,with grater conicity, of the dropper nozzle and the third portion (12)with a greater thickness than the two previous portions, is locatedclose to the mouth of the dropper nozzle (5), and comprises an annularprojection (13) intended to block the tubular sleeve (9) on the droppernozzle (5), in such a way as to prevent it from slipping off. Said blockis carried out with the cooperation with the tubular protective element(14), as it is more clearly shown in FIG. 11.

The tubular protective element (14), individually shown in FIGS. 6A-C,is in practise a roughly cylindrical component which is place around thedropper nozzle (5), or better around the tubular sleeve (9), in order toprotect it from accidental contacts during the use of the dispenser. Asit is more clearly shown in FIGS. 2 and 11, the presence of such rigidelement around the dropper (5) protects the elastomeric sleeve (9) fromany contact, so that its working, and therefore the accuracy anduniformity of the dosage of product drops through it is no disturbed byaccidental mechanical interference.

As it is shown both in FIGS. 10 and 11 and in FIG. 2, the tubularprotective element (14) is provided with the flange (15) in anintermediate position along its length, by which the said elementfixedly engages the closure element (4) of the dropper assembly (2).

The fourth component present in the dropper assembly (2) shown consistof a venting valve (16) with hydrophobic membrane, individually shown inthe FIGS. 7A and 7B, which in the embodiment shown consists of a Gore™valve, provided in its port with a membrane of 0.2 μm of porosity whichallows the passage of air through it but not the passage of liquid, andtherefore allows the bottle to be refilled with the volume of air equalto the volume dispensed product, while maintaining the total sterilityof the product contained and of the environment coming into contact withsaid product.

In order to complete the packaging and isolate the dropper from theexterior, the dispenser according to the invention is provided with aclosure capsule (3) (visible in FIG. 1 and, individually in FIG. 3),which comprises two overlapping and cooperating elements. Such elementsindividually shown in FIGS. 8A-C and in FIGS. 9A-C consists of a screwcap (17) having the internal thread (18) complementary to the thread(19) provided on the neck of the closure element (4) (see FIG. 3) and ofan externally knurled overcap (20).

In the case of the device proposed according the invention, however, thecapsule (3), or better, the cap (17) internal to said capsule (3) (whichis shown without he corresponding the external overcap in FIG. 10), alsocarries out the important function of cooperating with the elastomericsleeve (9) in mechanically blocking the ports (8) provided on theintermediate portion (7) with the grater conicity of the dropper nozzle(5). Actually, the cylindrical projection (21) of the cap (17) (see, inparticular FIGS. 3 and 8A) is shaped with suitable size for the cap(17), to abut with said projection, when the dispenser is closed,exactly on the intermediate portion (11) of the tubular sleeve (9), thatis the portion which covers the intermediate portion (7) with graterconicity of the dropper nozzle (5), wherein the ports (8) for thepassage of product from the interior of the bottle towards the exteriorare provided.

The position of the cylindrical projection (21) of the cap (17), whenthe dispenser is closed, has the advantage of not mechanicallyinterfering within elastomeric sleeve (9) present on the terminalportion (6) of the dropper nozzle (5), so that the said zone of thesleeve does not undergo any disturbance, damage or retraction due to thecontact with the cap (17). On the contrary, the point of contact isdisplaced to a zone where the elastomeric sleeve (9) is less subject tostress and, if needed it could also be realized with greater thickness.In addition, the cooperation between the dropper nozzle (5) and thecylindrical projection (21) of the cap (17), right in the portion wherethe ports (8) for the passage of the product are present, guaranteesagainst accidental leakage of the product which may originate fromuncontrolled pressures on the container body (1).

In addition, the illustrated capsule device (3) comprises a particularmechanical coupling between the cap (17) and the external overcap (20)(see FIGS. 8A-C and 9A-C) which constitutes a safety closure devicepreventing the dispenser from being opened by children (“child-proof”device). The over-cap (20) also comprises a tear-off removable collar(22) having function of guarantee seal (tamper-evident). The latterdemonstrates, by being unbroken at the moment of the first opening, thatdispenser is still sealed and has not been tampered with.

As it may be deduced from the above description, the dispenser accordingto the invention may be used in the same way as any normal dispenser forrepeated administration of a product, and does not require any specificprocedure for its use, but guarantees an immediate and automatic closureof the dropper when the user stops dispensing the product. This type ofstable, safe, sterile and automatic closure occurs at the tip of thedropper, where the dropper nozzle is located and this guarantees thecomplete sterility of the product, its storage without any oxidativephenomena and its availability for repeated administrations up to thecomplete emptying of the bottle contents.

Moreover, the device is easy to use also by the most inexperienced orelderly users and allows to supply a pharmaceutical product in exactlymetered drops, without giving rise to jets or sprays in the event thatthe dispenser is too energetically squeezed.

Finally, the structure of the proposed device is such that it is notexcessively complex but it is extremely simple to produce from amanufacturing standpoint with a reduced number of pieces, some of whichare the same as in the manufacturing lines already in use, for instancefor the production of similar liquid products in bottles with theaddition of preservatives. The dispenser according to the invention,therefore, appears to be extremely advantageous from the standpoint ofthe manufacturing flexibility of the corresponding apparatus.

The present invention has been disclosed with particular reference tosome specific embodiments thereof, but it should be understood thatmodifications and changes may be made by the persons skilled in the artwithout departing from the scope of the invention as defined in theappended claims.

1. A dispenser for liquid preparations without preservatives, comprisinga container body (1), a dropper assembly (2), and a closure capsule (3)suitable to be coupled with said dropper assembly (2), wherein thedropper assembly (2), in turn, comprises a closure element (4) for thecontainer body (1) ending with a rigid dropper nozzle (5) provided withone or more transversal passage ports (8), communicating with theinterior of said container body covered with a resiliently deformabletubular sleeve (9), cooperating with said ports (8) for intercepting aliquid preparation contained in said dispenser, characterized in thatthe said dropper nozzle (5) comprises at least two portions to axiallysubsequent portions having different conicity: a first portion withsmaller conicity (6) making out the distal end of said dropper nozzle(5) and a second portion with grater conicity (7) on which said two ormore ports (8) are provided, and in that said closure capsule comprisesan internal projection (21) that comes into contact, when the capsule isclosed, with said resiliently deformable tubular sleeve (9) at aposition corresponding to the second portion of the dropper nozzle (5)with grater conicity (7), thereby blocking the possible passage of theliquid preparation through the said two or more ports (8).
 2. Adispenser according to claim 1, wherein said said dropper assembly (2)further comprises a tubular protective element (14) coaxial with thesaid dropper nozzle (5), which extending outside said tubular sleeve (9)in such a way as to surround it for most of its length.
 3. A dispenseraccording to claim 1 or 2, wherein said resiliently deformable tubularsleeve (9) comprises a first portion (10) and a second axiallysubsequent portion (11) and corresponding to said first and secondportions of the said dispensing nozzle.
 4. A dispenser according toclaim 3, wherein said resiliently deformable tubular sleeve (9)comprises, at its end facing to the container body (1), a third portion(12), having a greater thickness than the previous ones, ending in anannular projection (13).
 5. A dispenser according to claim 4, whereinsaid annular projection (13) is coupled with the end of the citedtubular protective element (14) facing towards the container body (1).6. A dispenser according to claim 5, wherein said tubular protectiveelement (14) is provided with an intermediate flange (15) which isfixedly blocked on said closure element (4) of the container body (1).7. A dispenser according to anyone of claims 1-6, wherein the said twoor more ports (8) provided on the said first portion with the greaterconicity (7) of said dispensing nozzle (5) are three in number, placedat 120° one from the other around the periphery of the nozzle.
 8. Adispenser according to anyone of claims 1-7, wherein the said containerbody (1), is a single-walled bottle type made of flexible resilientmaterial or is of the double-walled type with a collapsible internalcontainer and an air gap place there between, or it is of thesingle-walled collapsible tube type.
 9. A dispenser according to claim8, of the single-walled type made of flexible resilient material,wherein said dropper assembly (2) also comprises a venting valve (16)with a hydrophobic membrane for the passage of the gases only from andinto the bottle.
 10. A dispenser according to claim 9, wherein the saidhydrophobic membrane has a porosity of 0.2 μm.
 11. A dispenser accordingto claim 9 or 10, wherein said venting valve (16) with hydrophobicmembrane is housed in a suitable seat within said closure element (4) insaid container body (1).
 12. A dispenser according to any one of claims1-11, wherein said closure capsule (3) comprises a screw cap (17)suitable to protect said dropper assembly (2) and a knurled overcap (20)external to said screw cap (17) and connected thereto.
 13. A dispenseraccording to claim 12, wherein the coupling between the said cap (17)and said overcap (20) creates a safety closure system preventingchildren from opening the bottle (child-proof device).